Stimulation of tumor necrosis factor-α production by mycoplasmas and inhibition by dexamethasone in cultured astrocytes

Elevated levels of tumor necrosis factor-α (TNFα) and other cytokines and eicosanoids in the central nervous system (CNS) have been noted in several human neurologic diseases, including multiple sclerosis and AIDS dementia. Recently it was shown that glial cells, especially astrocytes, are a major source of cytokines and eicosanoids. In the present study we have shown that astrocytes derived from fetal rat brain triggered by mycoplasmas produce TNFα and prostaglandin E₂ (PGE₂). Addition of mycoplasma (Mycoplasma capricolum isoalted from sheep and M. fermentans KL-4 from human) at a concentration of 1-50 μg protein/ml (2 × 10⁷-10⁹ colony forming units/ml), as well as lipopolysaccharide (5 μg/ml), led to a 200-500-fold increase in TNFα and a 2.5-4.5-fold increase in PGE₂ production. Preincubation of the cells with the synthetic glucocorticoid, dexamethasone (2 × 10^-5-2 × 10^-8M), as well as with the natural hormone, corticosterone, markedly inhibit the secretion of both TNFα and PGE₂. Thus, mycoplasmas can be added to the wide variety of agents that stimulate glial cells to produce cytokines and eicosanoids, and may contribute to various CNS pathological manifestations. In addition, the ability of glucocorticoids to inhibit particularly the stimulated productions of TNFα and PGE₂ may explain at least in part the therapeutic benefit of these agents in CNS inflammation and demyelination.